以降钙素基因高度甲基化为分子基因标志检测白血病微量残留病  

Hypermethylation of the calcitonin gene as molecular genetic marker in detecting minimal residual disease of leukemia

作　　者：唐义平[1] 邓承祺[2] 杜琼[1] 李戈[1] 曾昭惠[1] 张晋琳[1] 缪世锟[1] 成都 

机构地区：[1]四川省人民医院血液科 610072 [2]华西医科大学附属第一医院血液科

出　　处：《中华内科杂志》2001年第4期226-228,共3页Chinese Journal of Internal Medicine

摘　　要：目的　探讨以降钙素（ＣＴ）基因高度甲基化为白血病克隆的分子基因标志，检测白血病微量残留病（ＭＲＤ），并预测预后的可能性。方法　用限制性内切酶消化ＤＮＡ，应用聚合酶链反应（ＰＣＲ）技术检测２９例急性白血病（ＡＬ），其中急性淋巴细胞白血病（ＡＬＬ）１４例，急性非淋巴细胞白血病（ＡＮＬＬ）１５例和８例慢性粒细胞白血病（ＣＭＬ）急变患者的ＣＴ基因的甲基化程度。对ＣＴ基因高度甲基化阳性者，以ＣＴ基因高度甲基化为白血病克隆的分子基因标志，应用ＰＣＲ技术定期追踪检测骨髓ＭＲＤ。结果　ＡＬＬ中ＣＴ基因高度甲基化阳性率为８５．７％（１２／１４），ＡＮＬＬ为６０％（９／１５），ＣＭＬ急变为１００％（８／８），而对照组无一例阳性。２０例ＡＬ和ＣＭＬ急变患者完全缓解（ＣＲ）后均存在ＭＲＤ。ＣＲ后ＭＲＤ持续阳性或转阴后再次出现阳性，提示将发生骨髓复发，能提早２～１１个月预示疾病的复发。ＭＲＤ较早转阴并持续长期阴性者可能获得长期生存。结论　以ＣＴ基因高度甲基化为白血病克隆的分子基因标志，应用ＰＣＲ技术能起到监测白血病ＭＲＤ的作用，为预测白血病的预后开辟了一条新途径。Objective: To explore whether detecting minimal residual disease (MRD) of leukemia with hypermethylation of the calcitonin gene as molecular genetic marker of leukemic clone may predict the prognosis. Methods: Polymerase chain reaction (PCR) in combination with digestion of DNA with HpaⅡ was used to examine the methylation patterns of the calcitonin gene in 29 cases with acute leukemia and 8 cases with transformation of chronic myeloid leukemia. By using PCR, MRD was longitudinally detected in patients who were positive for hypermethylation of the calcitonin gene as molecular genetic marker. Results Twenty patients with acute leukemia and transformation of chronic myeloid leukemia had MRD after complete remission. Bone marrow relapse occurred soon when MRD persisted or reappeared. It may predict bone marrow relapse two to eleven months earlier. The patients who were negative for MRD early and remained persistently negative may acquire prolonged survival.Conclusion MRD of leukemia may be monitored by using PCR with hypermethylation of the calcitonin gene as molecular genetic marker for leukemic clone. It may prove useful in predicting the prognosis of leukemia.

关 键 词：白血病 残余肿瘤 降钙素 聚合酶链反应 高度甲基化 分子基因标志 MRD 

分 类 号：R733.7[医药卫生—肿瘤]